Almost a quarter of patients with treatment-refractory squamous cell carcinoma of the anal canal given nivolumab have shown a response

medwireNews: Phase II study findings point to a possible role for the anti-programmed death 1 (PD-1) agent nivolumab in patients with Squamous cell carcinoma of the anal canal (SCCA).

As reported in The Lancet Oncology,almost a quarter of the 37 patients with metastatic SCCA that had proven refractory to a median of two prior therapies achieved a RECIST-measured response to nivolumab, with the majority of responders achieving what the investigators describe as a “durable response”.

Stefano Cascinu, from the Università di Modena e Reggio Emilia in Italy, writes in a linked comment that “[f]or the first time in 20 years there is something new in the treatment of SCCA”.

However, he observes that while nivolumab “seems to greatly shrink tumours in 20–25% of patients”, the “bad news” is that the majority of patients did not benefit from the agent and while there were some Predictive markers, the researchers “could not propose a practical score to identify patients who would respond.”

The patients were given nivolumab 3 mg/kg every 2 weeks and, after a median of 10.1 months and six doses of the anti-PD-1 agent, 24% of the patients had a RECIST-measured response to treatment and 47% of the patients had stable disease, giving a disease control rate of 72%.

The two complete and seven partial responses reported included a response in one of the two HIV-positive patients, say Cathy Eng, from the University of Texas MD Anderson Cancer Center in Houston, USA, and co-investigators.

Of the patients who responded, 78% had a lasting response, at a median of 5.8 months, and 67% of these patients were still in the study at data cutoff, with 10.4 months the longest reported response.

Disease progression was reported in 65% of the patients during nivolumab treatment and 43% died from progression but there were no treatment-related deaths. Median progression-free survival was 4.1 months, with 38% achieving the 6-month checkpoint. Median overall survival was 11.5 months, with the 1-year rate estimated at 48%.

Gender, prior treatment with platinum chemotherapy or radiation, site of distant metastases and the most common mutations detected in the patients – TP53 and PIK3CA – were not linked to response to nivolumab.

But further analysis of tumour samples from 15 patients positive for human papillomavirus (HPV) indicated that the four responders had higher levels of T cells expressing CD8 than the nine nonresponders. These responders also had PD-L1 expression on around 40% of tumour cells, compared with around 10% for nonresponders.

“Although our tissue analysis was limited by a small number of specimens, these findings are consistent with data from other solid tumours such as melanoma,” write Cathy Eng et al.

Adverse events included anaemia (70%), fatigue (68%) and rash (30%); there were no grade 4 events but five patients experienced grade 3 events, including anaemia in two, and one case each of fatigue, rash and hypothyroidism.

Steroids and a break from nivolumab were required by one patient who developed treatment-related grade 2 pneumonitis, while another required immunosuppressive therapy for autoimmune hypothyroidism, which subsequently resolved.

“In summary, nivolumab is well tolerated, and is a promising treatment for patients with refractory metastatic SCCA”, the authors conclude.

“Based on these results, we remain optimistic that immune checkpoint blockade drugs represent the next step towards improving clinical outcomes for patients with this disease.”